'Nano' Medicine May Replace Insulin Shots

Researchers have developed a network of so-called "nanoparticles" that theoretically could be injected into the body and release insulin to counteract rising blood sugar levels in people with diabetes.

Tested so far in mice, the nano-network was able to maintain normal glucose levels for more than a week with a single injection. Currently, patients have to inject themselves with insulin several times a day to control their blood sugar levels.

"The main aim was to mimic the activity of the pancreas. In our system, when glucose levels go up, the nanoparticles degrade to release insulin," said study author Zhen Gu, from the joint department of biomedical engineering at the University of North Carolina at Chapel Hill and North Carolina State University. Gu, along with Robert Langer and Daniel Anderson, developed this technology when Gu was working at the Massachusetts Institute of Technology.

Although exciting, the research is very preliminary, one expert said.

"From a patient perspective, this could be incredible. It would reduce the burden of diabetes," said Sanjoy Dutta, senior director of treatment therapies at JDRF (formerly known as the Juvenile Diabetes Research Foundation). "But there are still lots of questions to be answered. This was a first-pass study."

This treatment would likely be most useful for people with type 1 diabetes, an autoimmune condition in which the pancreas no longer creates insulin. Insulin is a hormone that is needed to properly metabolize the carbohydrates in food. Because their bodies no longer produce insulin, people with type 1 diabetes must take multiple daily injections of insulin to replace the missing insulin so blood sugar levels stay steady.

Dutta said this treatment could also be helpful for people with type 2 diabetes who need to take insulin injections. People with type 2 diabetes still produce insulin, but their bodies don't use it efficiently.

There are many problems with existing insulin therapy. One is that you have to give yourself multiple injections every day. Another is that it's hard to figure out the exact dose of insulin you might need. Currently, people on insulin test their blood sugar by drawing a drop of blood from their fingertip numerous times a day, which lets them know whether they need more or less insulin in their next shot.

Someone with diabetes must also figure out how many carbohydrates are in the food they plan to eat. (Carbohydrates are broken down into sugar in the body to provide fuel for the cells in the body and brain.) If any of these calculations are wrong, blood sugar levels can go either too high or too low. Both extremes can be dangerous.

The nano-network is designed to deal with some of these issues. Insulin would be released in response to higher glucose levels, so there wouldn't be a need to check blood sugar levels so often. There also would be no need to count carbohydrates, because the nano-network would release insulin to process the food someone has eaten.

The nano-network is made up of nanoparticles with a solid core of insulin, modified dextran and glucose oxidase enzymes. In the presence of high glucose levels, the glucose oxidase enzymes convert glucose into gluconic acid. Gluconic acid, in turn, then dissolves the modified dextran, releasing the insulin.

The nano-network forms in the body after injection because some nanoparticles are coated with a negative charge, while others are given a positive charge. Once inside the body, these particles are attracted to each other and join together to form the nano-network, Gu said.

All of the components of the nano-network — and its byproducts — are completely biocompatible and dissolve over time, so they shouldn't cause any immune system response, Gu added.

The current study, published online this month in the journal ACS Nano, found that when injected into mice, the nano-network was able to control blood glucose levels for up to 10 days.

What remains to be seen is how the researchers will ensure that the nano-networks won't release too much insulin (causing low blood sugar levels) or not enough insulin (causing high blood sugar levels) in humans, and how someone would know when it was time for a new injection. Also, research with animals often can't be replicated in humans.

"This study demonstrates the idea. It's very promising, but we need to perform more studies," Gu said. "We want to further tailor the materials, and we want to increase the response speed of the insulin. It may take some time, but I'm quite confident in this new technology."

Dutta also was enthusiastic about the possibility of using glucose-responsive nano-networks. But, he cautioned, "This is going to take time. Many questions still need to be answered in animal studies, and we don't know what the regulatory pathway would be, although I do anticipate regulatory challenges. This is an uncharted pathway."

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